精子相关抗原6(SPAG6)是衣藻PF16的哺乳动物直向同源物,这是一种参与鞭毛运动的轴突中央对蛋白。在老鼠身上,已经鉴定了两个Spag6基因。祖先的基因,在小鼠2号染色体上,被命名为Spag6。最初称为Spag6的相关基因位于小鼠16号染色体上,是从古老的Spag6基因进化而来的。它已更名为类似Spag6(Spag6l)。Spag6编码由11个外显子组成的1.6kb转录本,而Spag6l编码2.4kb的转录物,其在3'端含有额外的非编码外显子以及在Spag6中发现的11个外显子。两个Spag6基因在它们的核苷酸和氨基酸序列中具有高度相似性。与Spag6lmRNA不同,这是广泛表达的,Spag6mRNA表达仅限于较少数量的组织,包括睾丸和大脑.在转染的哺乳动物细胞中,SPAG6/GFP位于微管上,与SPAG6L类似的本地化。先前产生了全局Spag6l敲除小鼠模型。除了调节纤毛搏动的作用外,SPAG6L有许多意想不到的功能,包括在调节纤毛发生/精子发生中的作用,听力,和免疫突触,在其他人中。探讨古Spag6基因的作用,我们对Spag6基因敲除小鼠进行表型分析。所有纯合突变小鼠都非常正常,男性和女性的生育力都没有受到影响。纯合雄性精子参数正常,包括精子数量,运动性,和形态学。睾丸组织学检查显示精子发生正常。选定的SPAG6L结合伴侣的睾丸蛋白表达水平,包括SPAG16L,在Spag6基因敲除小鼠中没有改变,尽管在Spag6l敲除小鼠中SPAG16L水平显著降低。两种SPAG6蛋白的结构分析表明,两者都采用非常相似的折叠,一些氨基酸的差异,其中许多是溶剂暴露的。这些差异赋予了两种蛋白质不同的功能特性,即使两者都有8个Armadillo重复序列介导蛋白质-蛋白质相互作用。我们的研究表明,SPAG6和SPAG6L在体内具有不同的功能,进化出的SPAG6L蛋白更重要。由于这两种蛋白质有一些重叠的结合伴侣,SPAG6可能具有尚未确定的功能。
Sperm-associated antigen 6 (SPAG6) is the mammalian orthologue of Chlamydomonas PF16, an axonemal central pair protein involved in flagellar motility. In mice, two
Spag6 genes have been identified. The ancestral gene, on mouse chromosome 2, is named
Spag6. A related gene originally called
Spag6, localized on mouse chromosome 16, evolved from the ancient
Spag6 gene. It has been renamed
Spag6-like (Spag6l). Spag6 encodes a 1.6 kb transcript consisting of 11 exons, while Spag6l encodes a 2.4 kb transcript which contains an additional non-coding exon in the 3\'-end as well as the 11 exons found in Spag6. The two Spag6 genes share high similarities in their nucleotide and amino acid sequences. Unlike Spag6l mRNA, which is widely expressed, Spag6 mRNA expression is limited to a smaller number of tissues, including the testis and brain. In transfected mammalian cells, SPAG6/GFP is localized on microtubules, a similar localization as SPAG6L. A global Spag6l knockout mouse model was generated previously. In addition to a role in modulating the ciliary beat, SPAG6L has many unexpected functions, including roles in the regulation of ciliogenesis/spermatogenesis, hearing, and the immunological synapse, among others. To investigate the role of the ancient
Spag6 gene, we phenotyped global
Spag6 knockout mice. All homozygous mutant mice were grossly normal, and fertility was not affected in both males and females. The homozygous males had normal sperm parameters, including sperm number, motility, and morphology. Examination of testis histology revealed normal spermatogenesis. Testicular protein expression levels of selected SPAG6L binding partners, including SPAG16L, were not changed in the Spag6 knockout mice, even though the SPAG16L level was significantly reduced in the Spag6l knockout mice. Structural analysis of the two SPAG6 proteins shows that both adopt very similar folds, with differences in a few amino acids, many of which are solvent-exposed. These differences endow the two proteins with different functional characteristics, even though both have eight armadillo repeats that mediate protein-protein interaction. Our studies suggest that SPAG6 and SPAG6L have different functions in vivo, with the evolved SPAG6L protein being more important. Since the two proteins have some overlapping binding partners, SPAG6 could have functions that are yet to be identified.